The techniques of voltage clamp and current clamp have made significant contributions to the understanding of complex current-voltage relations in excitable membranes. The recently developed dynamic clamp incorporates a computer in the feedback loop to impose a mathematical relation (conductance) between current and voltage. Our objective is to develop an innovative new technology instrument, the Universal Clamp, with enhanced capabilities for studying electrophysiology of nerve, muscle, and other excitable tissues. The implementation of feedback algorithms in computer software has provided a new dimension for electrophysiological studies, allowing for innovative experimental protocols such as sophisticated pulse sequencing and dynamic switching of clamp mode. However, as demonstrated by a simulation study in this proposal, processing delay introduced by the computer can result in significant performance degradation. The few existing implementations of dynamic clamps have been based on off-the-shelf devices, not optimized for digital feedback; in particular, they do not provide an adequate frequency response for studying fast action potentials. To successfully clamp a fast action potential with digital feedback, the system throughput needs to be as high as 500 KHz to 1 MHz. Such high-throughput systems have recently become feasible with the introduction of faster digital signal processing (DSP) chips and appropriate control algorithms. Therefore, this project is designed to develop 1) analog electronics optimized for digital feedback control of excitable membranes; 2) customized DSP software for maximized throughput (1 MHz), advanced digital tracking, and ease of use; and 3) a unified multi-channel system capable of voltage clamp, current clamp, conductance clamp, and forming neuronal networks with computer-simulated synapses. During the development, the Universal Clamp will be tested on cardiac muscles of the surf clam with a double-sucrose-gap preparation and cerebral ganglion neurons of the pond snail with two microelectrodes. The Universal Clamp represents a new generation DSP-based instrument for electrophysiological studies. The instrument will be versatile, flexible, and cost-effective; and will lead to new frontiers in neuroscience research. The digital feedback control in the proposed Universal Clamp will also lend itself to exploratory applications such as brain-machine interface, neuromuscular control of prosthetic devices, and artificial sensory replacements and implants. [unreadable] [unreadable] [unreadable]